Our previous studies demonstrated that Alpha-MSH, which has a widespread immunohistochemical distribution in nerve fiber throughout the hypothalamus, increased heart rate (HR) when injected into the rostral dorsomedial hypothalamic nucleus (DM) but not in other sites in the hypothalamus. Studies on the central cardio-vascular (CV) effects of other neuropeptides suggest multiple sites of CV activity within the hypothalamus, which is in agreement with electrical stimulation data. For example, the potent opiate receptor agonist, dermorphin (40 pmol) produced increases in HR with minimal increases in blood pressure (BP) when injected into the anterior hypothalamic nucleus (AH). The response appears to be mediated through opiate receptors, and the mechanism involves activation of cardiac sympathetic nerves. Thyroid releasing hormone (TRH) also causes an increase in HR but not BP in the AH and the mechanism also appears to be activation of cardiac sympathetic nerves as indicated for dermorphin above. In addition, TRH (1.4 pmol) causes increases in BP and HR from sites in the preoptic suprachiasmatic nucleus (POS), a response which appears to be due to a more general activation of the sympathetic nervous system and may include vagal withdrawal as a component of the increased HR. TRH has modest tachycardic effects in parts of the medial preoptic nucleus (POM) and in the DM and posterior hypothalamic nucleus (PH). Bradykinin resembles TRH in its site-dependent actions; increases in BP and HR in the DM and PH, tachycardia in the POS and POM and bradycardia in the PVN. Importantly, with each peptide, the CV responses were obtained in areas of the hypothalamus that have been reported to contain receptors and/or immunocytochemical evidence of fibers and cells containing the peptide. However, not all hypothalamic areas containing a given peptide responded with CV changes when the peptide was injected. General findings with all peptides tested were a relatively long duration of action (40 min to greater than 90 min) and tachyphylaxis to repeated injections.